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Ossifying renal tumor of infancy (ORTI): A case report and review of the literature
Journal of Pediatric Surgery (2013) 48, E37–E40
www.elsevier.com/locate/jpedsurg
Ossifying renal tumor of infancy (ORTI): A case report and review of the literature Jimeng Hu a , Yeming Wu a,⁎, Jun Qi b , Chi Zhang a , Fan Lv a a
Department of Pediatric Surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China b Department of Urology, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China Received 10 October 2012; revised 9 December 2012; accepted 10 December 2012
Key words: Ossifying renal tumor of infancy (ORTI); Renal tumor; Diagnosis
Abstract We present the case of a 6-month-old boy who was referred to us with the chief complaint of intermittent painless gross hematuria. Computed tomography (CT) scan of the abdomen showed a partially calcified soft-tissue mass that was located in the lower pole of the right kidney and extended into the collecting system. Consequently, a partial nephrectomy was performed. The resected specimen showed that the tumor was partially calcified and occupied the renal pelvis. The histological findings suggested a diagnosis of ossifying renal tumor of infancy (ORTI), only 16 cases of which have been reported in the literature. The pathogenesis of this condition has not been well established. ORTI should be considered in the differential diagnosis for infants with gross hematuria and a calcified mass in the pelvicalyceal system. © 2013 Published by Elsevier Inc.
Ossifying renal tumor of infancy (ORTI) was first described by Chatten et al. in 1980 as a variant of pediatric renal tumors [1]. ORTI is an extremely rare, benign renal tumor with typical clinical, radiological, and pathological features. Gross hematuria is always observed in ORTIs, and magnetic resonance imaging (MRI) and computed tomography (CT) aid in diagnosis. However, a definitive diagnosis can only be made on the basis of pathological data. Herein, we report a rare case of ORTI that we encountered at our hospital and summarize the findings of the 16 cases reported in the literature. We expect that our retrospective analysis of these cases will help improve the rate of accurate diagnosis. ⁎ Corresponding author. Department of Pediatric Surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China. Tel.: +86 130 031 78888. E-mail address: [email protected] (Y. Wu). 0022-3468/$ – see front matter © 2013 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jpedsurg.2012.12.020
1. Case report Our patient was a 6-month-old boy with the chief complaint of intermittent painless gross hematuria for 2 months. The boy did not show any other clinical symptoms such as fever or dysuria and no related abnormalities. Physical examination showed no painful abdominal mass palpable in the upper quadrant. The patient's white blood cell (WBC) count was 7600/mm3, C-reactive protein level was 6.0 mg/dL, and hemoglobin level was 9.9 mg/dL. Urinalysis results showed numerous red blood cells per high-power field, a corpuscular hemoglobin level of 250/μL and a urine protein level of 25.0 mg/dL. Renal and hepatic function and electrolyte examinations yielded normal results. Ultrasonography examination showed a solid mass in the lower pole of the right kidney, which indicated that the tumor may have
E38
Fig. 1 Unenhanced Computed tomography (CT) illustrated a calcified renal hamartomatous soft tissue mass in the lower pole of right kidney.
originated from the renal sinus; no obvious hydronephrosis or ureter dilatation was seen. Abdominal CT examination showed a partially calcified soft-tissue mass that was located
J. Hu et al. in the lower pole of the right kidney and extended into the collecting system (Fig. 1). The diagnosis of a renal tumor growing into the collecting system was confirmed, and a partial nephrectomy was performed using a transabdominal approach. During the operation, we found a 3 cm × 2 cm × 1.5 cm rock-hard mass located in the lower pole; the mass extended to the renal pelvis and entirely filled the calyceal space of the right kidney (Fig. 2). A right lower pole nephrectomy was performed in which the tumor was completely resected (Fig. 2) and two-thirds of the kidney was spared. Surgical hypothermia was established immediately after renal artery clamping and maintained for 10 min to decrease core temperature before starting the tumor resection. After complete excision of the tumor, closure of the renal defect with adjacent fat, fascia, peritoneum, and water-tight closure of the collecting system with fine absorbable sutures were performed. In this manner the tumor resection was achieved with preservation of the renal pelvis. Pathological examination led to a diagnosis of ORTI. Light microscopy showed that the tumor appeared to have ill-defined borders with the renal parenchyma and consisted
Fig. 2 During the operation (A, B), we found 3 cm × 2 cm × 1.5 cm rock-hard mass located in the lower pole of right kidney. Resected specimen (C, D) revealed an ossifying-like appearance that occupied the right renal pelvis.
Ossifying renal tumor of infancy
E39
of osteoid islands, osteoblast-like cells, and spindle cells. Immunohistochemistry analysis showed that the osteoblastlike cells moderately coexpressed vimentin, epithelial membrane antigen (EMA), and cytokeratin (CK) but did not express desmin. The spindle cells strongly expressed vimentin but did not express EMA or CK. More than 5% of the cells, most of which were spindle cells, expressed Ki-67. ORTI was diagnosed on the basis of the above clinical, imaging, and histological findings. During follow-up in outpatient service, we found that serum creatinine (Scr) measurement of the patient was normal. Glomerular filtration rate (GFR) was tested to evaluate the renal function of remaining kidney by using 99mTc-Diethylenetetramine pentaacetic acid (99mTc-DTPA) renal scan. The split renal function of right kidney was 35% according to the renal scan results. No local recurrence or metastasis was observed as of 6 months after the surgery.
2. Discussion ORTI is a very rare benign renal tumor of early infancy. To our knowledge, only 16 cases of ORTI have been reported in the literature [1–10]. In these published cases (Table 1), the minimum age was 6 days, the maximum age was 2 years and 6 months, and the average age was 5.5 months. Of the 16 patients, 12 were male patients and 4 were female patients; in 12 patients, the tumor occurred on the left side of the urinary system and in 4 patients, the tumor occurred on the right side. The largest tumors were located in the kidney pole and extended into the renal calyx and renal pelvis, with 11 in the upper pole of the kidney, 4
Table 1
in the lower pole, and 1 in the renal pelvis. No case of bilateral ORTI has been reported yet. In 15 of these 16 cases, the first symptom was gross hematuria (including 1 case with hydronephrosis), while an abdominal mass was observed in 1 case [7]. Laboratory tests, including blood and biochemical tests, yielded normal results. In most of the above reports, intravenous pyelography (IVP) showed an intrarenal lumpy high-density mass; CT showed intratumoral calcification, much like staghorn calculi, in the pelvis and calyces. The patient discussed in this article had clinical features similar to those discussed above. Histological analysis showed that 3 major components – an osteoid core, osteoblast-like cells, and spindle cells – were present in all lesions. The most proportion of the tumor including osteoblast-like cells with osteoid matrix that emerged focally calcified. Cyst formation can be observed at the periphery of the osteoid matrix for such tumors [7]. There was no proof of mitoses or atypia. Local tumor tissue plunge into the collection tube and proliferative changes can sometimes be seen in luminal epithelial cells [6]. Immunohistochemical analysis showed that the spindle cells strongly expressed vimentin but did not express EMA or CK. Polygonal cells expressed vimentin, EMA, desmin, and CK. Neither spindle cells nor polygonal cells expressed neuron-specific enolase, chromogranin A, or smooth muscle actin [5,6]. Electron microscopy analysis indicated that the polygonal cells showed characteristics of epithelial differentiation, including microtubule formation, tight junctions, and desmosome emergence. Interzonal fibers and the expansion of granular endoplasmic reticulum are visible in the cytoplasm in such cases. Lacson reported that the characteristics of osteoblast-like cells were a cross between those of fibroblasts and epithelial cells [8].
Ossifying renal tumor of infancy (ORTI) reported in the article.
No.
Age
Gender
Symptom
Side
Size (cm)
Image
Treatment
Follow-up
1 2 3 4 5 6 7 8 9 10 11
4 mo 3 mo 6d 6 mo 11 mo 14 mo 2.5 mo 3 mo 2.5 mo 4 mo 10 mo
M M M M F M M M M M F
GH GH GH GH GH GH GH GH GH GH AM
L L L L L L L R L R L
2–3 2–3 2 1.8 3 2 2 3 2.5 1 2.5
partial nephrectomy + chemotherapy nephrectomy + chemotherapy nephrectomy nephrectomy partial nephrectomy nephrectomy nephrectomy + chemotherapy nephrectomy nephrectomy nephrectomy partial nephrectomy
7y 2.3 y 1.7 y 2y 1.6 y 12.5 y 11.5 y 0.7 y 0.7 y 23.6 y 2y
12 13 14 15 16
4 mo 10 mo 30 mo 2 mo 7 mo
M F M M F
GH+AM GH GH GH GH
R L R L L
3 3 2 2.3 2.5
calcification calcification no calcification calcification calcification calcification no calcification calcification calcification calcification calcification + Hydronephrosis calcification calcification calcification calcification calcification
nephrectomy nephrectomy partial nephrectomy partial nephrectomy partial nephrectomy
5.3 y 2.5 y 1.6 y 0.8 y 2y
M=Male, F=Female, GH = Gross Hematuria, AM = Abdominal Mass, mo=month(s), y=year(s), L=Left, R=Right.
E40 The histogenesis of ORTI remains unclear, but the information available on its pathogenesis shows that it is a subtype of congenital mesoblastic nephroma, shows growth features characteristic of an intralobar nephrogenic rest, and may arise from the urinary tract epithelium rather than the renal parenchyma [3,5,6]. The diagnosis of ORTI is based primarily on the following: (1) infant age; (2) gross hematuria as the main clinical manifestation; (3) detection on imaging (IVP, CT); (4) 3 major components—an osteoid core, osteoblast-like cells, and spindle cells; (5) immunohistochemical results showing that the spindle cells strongly express vimentin and osteoblast-like cells express vimentin and EMA; and (6) electron microscopy results showing polygonal cells with characteristics of epithelial differentiation. ORTI is a benign renal tumor, and the best treatment approach for this tumor involves intraoperative retention of kidney tissue. Surgical methods, including partial nephrectomy and tumor resection after pelvic incision, should be based on the tumor location. To increase the diagnostic accuracy for ORTI, doctors should base the preliminary diagnosis on clinical manifestations and imaging features to reduce the probability of nephrectomy.
J. Hu et al.
References [1] Chatten J, Cromie WJ, Duckett JW. Ossifying tumor of infantile kidney: report of two cases. Cancer 1980;45:609-12. [2] Jerkins GR, Callihan TR. Ossifying renal tumor of infancy. J Urol 1986;135:120-1. [3] Middlebrook PF, Jimenez CL, Schillinger JF. Ossifying renal tumor of infancy: a case report. J Urol 1992;147:1337-9. [4] Steffens J, kraus J, Misho B, et al. Ossifying renal tumor of infancy. J Urol 1993;149:1080-1. [5] Sotelo-Avila C, Beckwith JB, Johnson JE. Ossifying renal tumor of infancy: a clinicopathologic study of nine cases. Pediatr Pathol Lab Med 1995;15:745-62. [6] Ito J, Shinohara N, Koyanagi T, et al. Ossifying renal tumor of infancy: the first Japanese case with long-term follow-up. Pathol lnt 1998;48: 151-9. [7] Vazquez JL, Barnewolf CE, Shamberger RC, et al. Ossifying renal tumor of infancy presenting as a palpable abdominal mass. Pediatr Radio 1998;28:454-7. [8] Lacson AC, Homsy YL, Benator R. Ossifying renal tumor of infancy. Presented at the college of American pathologists 2003 Annual Meeting. Arch Pathol Lab Med 2004;128:139-40. [9] El-Husseini TK, Egail SA, Al-Orf AM, et al. Ossifying renal tumor of infancy. Saudi Med J 2005;26:1978-89. [10] Schelling J, Schroder A, Stein R, et al. Ossifying renal tumor of infancy. J Pediatr Urol 2007;3:258-61.
www.elsevier.com/locate/jpedsurg
Ossifying renal tumor of infancy (ORTI): A case report and review of the literature Jimeng Hu a , Yeming Wu a,⁎, Jun Qi b , Chi Zhang a , Fan Lv a a
Department of Pediatric Surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China b Department of Urology, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China Received 10 October 2012; revised 9 December 2012; accepted 10 December 2012
Key words: Ossifying renal tumor of infancy (ORTI); Renal tumor; Diagnosis
Abstract We present the case of a 6-month-old boy who was referred to us with the chief complaint of intermittent painless gross hematuria. Computed tomography (CT) scan of the abdomen showed a partially calcified soft-tissue mass that was located in the lower pole of the right kidney and extended into the collecting system. Consequently, a partial nephrectomy was performed. The resected specimen showed that the tumor was partially calcified and occupied the renal pelvis. The histological findings suggested a diagnosis of ossifying renal tumor of infancy (ORTI), only 16 cases of which have been reported in the literature. The pathogenesis of this condition has not been well established. ORTI should be considered in the differential diagnosis for infants with gross hematuria and a calcified mass in the pelvicalyceal system. © 2013 Published by Elsevier Inc.
Ossifying renal tumor of infancy (ORTI) was first described by Chatten et al. in 1980 as a variant of pediatric renal tumors [1]. ORTI is an extremely rare, benign renal tumor with typical clinical, radiological, and pathological features. Gross hematuria is always observed in ORTIs, and magnetic resonance imaging (MRI) and computed tomography (CT) aid in diagnosis. However, a definitive diagnosis can only be made on the basis of pathological data. Herein, we report a rare case of ORTI that we encountered at our hospital and summarize the findings of the 16 cases reported in the literature. We expect that our retrospective analysis of these cases will help improve the rate of accurate diagnosis. ⁎ Corresponding author. Department of Pediatric Surgery, Xinhua hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China. Tel.: +86 130 031 78888. E-mail address: [email protected] (Y. Wu). 0022-3468/$ – see front matter © 2013 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jpedsurg.2012.12.020
1. Case report Our patient was a 6-month-old boy with the chief complaint of intermittent painless gross hematuria for 2 months. The boy did not show any other clinical symptoms such as fever or dysuria and no related abnormalities. Physical examination showed no painful abdominal mass palpable in the upper quadrant. The patient's white blood cell (WBC) count was 7600/mm3, C-reactive protein level was 6.0 mg/dL, and hemoglobin level was 9.9 mg/dL. Urinalysis results showed numerous red blood cells per high-power field, a corpuscular hemoglobin level of 250/μL and a urine protein level of 25.0 mg/dL. Renal and hepatic function and electrolyte examinations yielded normal results. Ultrasonography examination showed a solid mass in the lower pole of the right kidney, which indicated that the tumor may have
E38
Fig. 1 Unenhanced Computed tomography (CT) illustrated a calcified renal hamartomatous soft tissue mass in the lower pole of right kidney.
originated from the renal sinus; no obvious hydronephrosis or ureter dilatation was seen. Abdominal CT examination showed a partially calcified soft-tissue mass that was located
J. Hu et al. in the lower pole of the right kidney and extended into the collecting system (Fig. 1). The diagnosis of a renal tumor growing into the collecting system was confirmed, and a partial nephrectomy was performed using a transabdominal approach. During the operation, we found a 3 cm × 2 cm × 1.5 cm rock-hard mass located in the lower pole; the mass extended to the renal pelvis and entirely filled the calyceal space of the right kidney (Fig. 2). A right lower pole nephrectomy was performed in which the tumor was completely resected (Fig. 2) and two-thirds of the kidney was spared. Surgical hypothermia was established immediately after renal artery clamping and maintained for 10 min to decrease core temperature before starting the tumor resection. After complete excision of the tumor, closure of the renal defect with adjacent fat, fascia, peritoneum, and water-tight closure of the collecting system with fine absorbable sutures were performed. In this manner the tumor resection was achieved with preservation of the renal pelvis. Pathological examination led to a diagnosis of ORTI. Light microscopy showed that the tumor appeared to have ill-defined borders with the renal parenchyma and consisted
Fig. 2 During the operation (A, B), we found 3 cm × 2 cm × 1.5 cm rock-hard mass located in the lower pole of right kidney. Resected specimen (C, D) revealed an ossifying-like appearance that occupied the right renal pelvis.
Ossifying renal tumor of infancy
E39
of osteoid islands, osteoblast-like cells, and spindle cells. Immunohistochemistry analysis showed that the osteoblastlike cells moderately coexpressed vimentin, epithelial membrane antigen (EMA), and cytokeratin (CK) but did not express desmin. The spindle cells strongly expressed vimentin but did not express EMA or CK. More than 5% of the cells, most of which were spindle cells, expressed Ki-67. ORTI was diagnosed on the basis of the above clinical, imaging, and histological findings. During follow-up in outpatient service, we found that serum creatinine (Scr) measurement of the patient was normal. Glomerular filtration rate (GFR) was tested to evaluate the renal function of remaining kidney by using 99mTc-Diethylenetetramine pentaacetic acid (99mTc-DTPA) renal scan. The split renal function of right kidney was 35% according to the renal scan results. No local recurrence or metastasis was observed as of 6 months after the surgery.
2. Discussion ORTI is a very rare benign renal tumor of early infancy. To our knowledge, only 16 cases of ORTI have been reported in the literature [1–10]. In these published cases (Table 1), the minimum age was 6 days, the maximum age was 2 years and 6 months, and the average age was 5.5 months. Of the 16 patients, 12 were male patients and 4 were female patients; in 12 patients, the tumor occurred on the left side of the urinary system and in 4 patients, the tumor occurred on the right side. The largest tumors were located in the kidney pole and extended into the renal calyx and renal pelvis, with 11 in the upper pole of the kidney, 4
Table 1
in the lower pole, and 1 in the renal pelvis. No case of bilateral ORTI has been reported yet. In 15 of these 16 cases, the first symptom was gross hematuria (including 1 case with hydronephrosis), while an abdominal mass was observed in 1 case [7]. Laboratory tests, including blood and biochemical tests, yielded normal results. In most of the above reports, intravenous pyelography (IVP) showed an intrarenal lumpy high-density mass; CT showed intratumoral calcification, much like staghorn calculi, in the pelvis and calyces. The patient discussed in this article had clinical features similar to those discussed above. Histological analysis showed that 3 major components – an osteoid core, osteoblast-like cells, and spindle cells – were present in all lesions. The most proportion of the tumor including osteoblast-like cells with osteoid matrix that emerged focally calcified. Cyst formation can be observed at the periphery of the osteoid matrix for such tumors [7]. There was no proof of mitoses or atypia. Local tumor tissue plunge into the collection tube and proliferative changes can sometimes be seen in luminal epithelial cells [6]. Immunohistochemical analysis showed that the spindle cells strongly expressed vimentin but did not express EMA or CK. Polygonal cells expressed vimentin, EMA, desmin, and CK. Neither spindle cells nor polygonal cells expressed neuron-specific enolase, chromogranin A, or smooth muscle actin [5,6]. Electron microscopy analysis indicated that the polygonal cells showed characteristics of epithelial differentiation, including microtubule formation, tight junctions, and desmosome emergence. Interzonal fibers and the expansion of granular endoplasmic reticulum are visible in the cytoplasm in such cases. Lacson reported that the characteristics of osteoblast-like cells were a cross between those of fibroblasts and epithelial cells [8].
Ossifying renal tumor of infancy (ORTI) reported in the article.
No.
Age
Gender
Symptom
Side
Size (cm)
Image
Treatment
Follow-up
1 2 3 4 5 6 7 8 9 10 11
4 mo 3 mo 6d 6 mo 11 mo 14 mo 2.5 mo 3 mo 2.5 mo 4 mo 10 mo
M M M M F M M M M M F
GH GH GH GH GH GH GH GH GH GH AM
L L L L L L L R L R L
2–3 2–3 2 1.8 3 2 2 3 2.5 1 2.5
partial nephrectomy + chemotherapy nephrectomy + chemotherapy nephrectomy nephrectomy partial nephrectomy nephrectomy nephrectomy + chemotherapy nephrectomy nephrectomy nephrectomy partial nephrectomy
7y 2.3 y 1.7 y 2y 1.6 y 12.5 y 11.5 y 0.7 y 0.7 y 23.6 y 2y
12 13 14 15 16
4 mo 10 mo 30 mo 2 mo 7 mo
M F M M F
GH+AM GH GH GH GH
R L R L L
3 3 2 2.3 2.5
calcification calcification no calcification calcification calcification calcification no calcification calcification calcification calcification calcification + Hydronephrosis calcification calcification calcification calcification calcification
nephrectomy nephrectomy partial nephrectomy partial nephrectomy partial nephrectomy
5.3 y 2.5 y 1.6 y 0.8 y 2y
M=Male, F=Female, GH = Gross Hematuria, AM = Abdominal Mass, mo=month(s), y=year(s), L=Left, R=Right.
E40 The histogenesis of ORTI remains unclear, but the information available on its pathogenesis shows that it is a subtype of congenital mesoblastic nephroma, shows growth features characteristic of an intralobar nephrogenic rest, and may arise from the urinary tract epithelium rather than the renal parenchyma [3,5,6]. The diagnosis of ORTI is based primarily on the following: (1) infant age; (2) gross hematuria as the main clinical manifestation; (3) detection on imaging (IVP, CT); (4) 3 major components—an osteoid core, osteoblast-like cells, and spindle cells; (5) immunohistochemical results showing that the spindle cells strongly express vimentin and osteoblast-like cells express vimentin and EMA; and (6) electron microscopy results showing polygonal cells with characteristics of epithelial differentiation. ORTI is a benign renal tumor, and the best treatment approach for this tumor involves intraoperative retention of kidney tissue. Surgical methods, including partial nephrectomy and tumor resection after pelvic incision, should be based on the tumor location. To increase the diagnostic accuracy for ORTI, doctors should base the preliminary diagnosis on clinical manifestations and imaging features to reduce the probability of nephrectomy.
J. Hu et al.
References [1] Chatten J, Cromie WJ, Duckett JW. Ossifying tumor of infantile kidney: report of two cases. Cancer 1980;45:609-12. [2] Jerkins GR, Callihan TR. Ossifying renal tumor of infancy. J Urol 1986;135:120-1. [3] Middlebrook PF, Jimenez CL, Schillinger JF. Ossifying renal tumor of infancy: a case report. J Urol 1992;147:1337-9. [4] Steffens J, kraus J, Misho B, et al. Ossifying renal tumor of infancy. J Urol 1993;149:1080-1. [5] Sotelo-Avila C, Beckwith JB, Johnson JE. Ossifying renal tumor of infancy: a clinicopathologic study of nine cases. Pediatr Pathol Lab Med 1995;15:745-62. [6] Ito J, Shinohara N, Koyanagi T, et al. Ossifying renal tumor of infancy: the first Japanese case with long-term follow-up. Pathol lnt 1998;48: 151-9. [7] Vazquez JL, Barnewolf CE, Shamberger RC, et al. Ossifying renal tumor of infancy presenting as a palpable abdominal mass. Pediatr Radio 1998;28:454-7. [8] Lacson AC, Homsy YL, Benator R. Ossifying renal tumor of infancy. Presented at the college of American pathologists 2003 Annual Meeting. Arch Pathol Lab Med 2004;128:139-40. [9] El-Husseini TK, Egail SA, Al-Orf AM, et al. Ossifying renal tumor of infancy. Saudi Med J 2005;26:1978-89. [10] Schelling J, Schroder A, Stein R, et al. Ossifying renal tumor of infancy. J Pediatr Urol 2007;3:258-61.